The innate immune system provides the first line of defense against broad ranges of pathogens and is evolutionally conserved between plants and animals. Delicate regulation of the immune response is essential for an organism's health and growth. Both positive and negative signaling pathways interplay to develop a balanced defense response with appropriate amplitude and duration. An Arabidopsis Nudix hydrolase (MPR1) which hydrolyzes nucleotide derivatives has recently been identified as a key mediator of the basal innate immune response. Loss of MPR1 function causes hyper-responsiveness to not only pathogenic strains but also non-pathogenic strains of Pseudomonas syringae. It is proposed that MPR1 may exert its role by sensing and modulating the level of a nucleotide derivative to fine-tune the defense response and prevent excessive cell stimulation. The proposed project aims to define the precise function of MPR1 in basal innate immunity and to identify additional players in plant innate immunity by employing a combination of molecular, genetic, biochemical, and functional genomics tools. The study will provide novel and important insights into molecular mechanisms that regulate the signaling pathway in basal innate immunity by achieving the following specific aims. (1) The mpr1 mutant and MPR1 protein will be characterized in detail to understand the definitive mechanism by which MPR1 modulates the defense response. (2) The mpr1 mutant will be used as a tool to understand roles of other genes in regulating innate immunity signaling. (3) Genetic, biochemical, and molecular approaches will be employed to identify additional components functioning in the basal immune response. In addtion, methods will be developed towards identifying physiological substrates of MPR1. The proposed study will not only advance our understanding of plants'innate immune responses but may also increase our knowledge of the mechanisms involved in the delicate control of immune responses in humans necessary to maintain good health. Elucidating the role of MPR1 in defense will also promote its use as a new tool for the genetic engineering of crops that have durable and broad-spectrum disease resistance which would reduce the use of chemicals for disease control, a big environmental and human health concern.